Macro-micro-autophagy

The importance of basic research has been highlighted this year by Yoshinori Ohsumi receiving the Nobel Prize in Medicine for his work on the process of autophagy. Autophagy—literally “self-eating”—is a fundamental cellular process that degrades and recycles cellular components. During autophagy, fatty capsules, or vesicles, form around internal components of a cell (autophagosomes), are fused with a lysosome, an acidic cellular compartment that breaks down its contents (this fused structure is called an autolysosome). Malfunctioning autophagy has been found to play roles in many conditions such as Parkinson’s, cancer, type II diabetes and metabolic disorders. Autophagy was first identified in the 1960’s, but the mechanisms and key genes controlling autophagy remained nebulous for another 30 years. It wasn’t until the 1990’s that Ohsumi and colleagues performed “mutagenesis screens” , in baker’s yeast that uncovered essential components of this process. Mutagenesis screens are used to discover genes involved in different biological processes: First, researchers induce random mutations in a model organism, then they look for individuals that are defective in the process they’re interested in, and finally, they identify the genes that were mutated in the affected individuals. These genes are likely to be important for the process under study, and this is exactly what Ohsumi did to elucidate the process of autophagy.

Dr. Katherine Rogers’ commentary on this award speaks to the impact of mutagenesis screens on our understanding of biology and how basic research can have broad applications. Dr. Rogers explains that mutagenesis screens have been crucial in identifying the key genes that regulate many different biological processes, which is an important first step in understanding how these processes work. In turn, improved understanding of basic biological processes often has far-reaching and unpredictable implications.

Concerning work in basic research, Dr. Rogers says that “great progress in applied science often comes from people studying relatively obscure things that don’t have evident intrinsic value to medicine/technology/etc. (GFP, PCR, lasers, and CRIPSR/CAS9 all came out of basic research where nobody was trying to cure a disease).” These technologies have been developed as powerful tools that have changed science, medicine, agriculture, and crime scene investigations, to name a few. Ultimately, Ohsumi’s work uncovered how the proteins involved in autophagy work together to create a cellular recycling and degradation system. This work, along with countless others, speaks to the importance of basic research and how it shapes our world.

Acknowledgements: Many thanks to Katherine Rogers, Developmental biologist at the Friedrich Miescher Laboratory of the Max Planck Society in Tübingen Germany, for her invaluable comments on the importance of this work.

Managing Correspondent: Aaron Aker

Media coverage:

Related SITN post: http://sitn.hms.harvard.edu/flash/2016/basic-research-understanding-way-things-work-matters/

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